That's a head-scratcher. Must be something serious. But even then, few players faced with something serious are willing to miss a big game. Don't know what his strengths are as a RB but wonder if another team would want him, if the Colts decided he's no longer a good fit for them.
Edit: Just speculation, but it seems perhaps his heart is no longer into football. Watching him even last season, he seemed to have a lot less tenacity carrying the ball compared to most RBs. Or was I just imagining it?